This invention relates to a method of preparing (threo)-1-Aryl-2-acylamido-3-fluoro-1-propanols. More particularly, this invention relates to preparing D-(threo)-1-Aryl-2-acylamido-3-fluoro-1-propanol antibacterial agents, including 3-fluoro-3-deoxy derivatives of chloramphenicol and of thiamphenicol. This invention also relates to cis-1-Aryl-2-(fluoromethyl)oxiranes, intermediates in the preparation of D,L-and D-(threo)-1-Aryl-2-acylamido-3-fluoro-1-propanols and to a method of preparing such intermediates.
D-(threo)-1-Aryl(phenyl or para-and/or meta-substituted phenyl)-2-acylamido-3-fluoro-1-propanols and racemic mixtures thereof are known in the art as broad spectrum antibacterial agents useful in the treatment of gram positive, gram negative and rickettsial infections. See, for example, U.S. Pat. Nos. 4,235,892, and 4,361,557.
U.S. Pat. No. 4,311,857 discloses methods of preparing D-(threo)-1-Aryl-2-acylamido-3-fluoro-1-propanols by reaction of D-(threo)-1-Aryl-2-N-protected-amino-1,3-propanediol with dialkylaminosulfur trifluoride followed by removal of the N-protecting group and thence reaction of the resulting D-(threo)-1-Aryl-2-amino-3-fluoro-1-propanol with a lower alkanoic acid derivative. However, the method uses an optically active starting material and it would be economically desirable to provide a synthetic pathway to (threo)-1-Aryl-2-acylamido-3-fluoro-1-propanols employing racemic starting materials and delay a resolution of the racemic mixture to a late step in the process.